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J B Natvig

Publications and source records attributed to J B Natvig.

At least 19 recordsLinked to original sources

Mycobacteria and human heat shock protein-specific cytotoxic T lymphocytes in rheumatoid synovial inflammation.

OBJECTIVE: To study the cytotoxic capacity of mycobacteria-specific T lymphocyte lines and clones from sites of inflammation in patients with rheumatoid arthritis (RA). We also studied antigen specificity, surface phenotype, expression of T cell receptors (TCR), and HLA restriction. METHODS: Autologous macrophages (M phi) from the synovial membrane (SM), synovial fluid (SF), or peripheral blood (PB) were used as target cells in cytotoxicity assays. RESULTS: All SM and SF cell lines tested thus far have shown specific lysis of the autologous M phi from SM or PB that had been pulsed with BCG (bacillus Calmette-Guerin), but no cytotoxicity when the targets were pulsed with irrelevant antigens such as tetanus toxoid and Chlamydia. Both CD4+ and CD8+ cells were shown to be involved in the specific cytolysis. The majority of the cytotoxic T lymphocyte (CTL) lines were TCR alpha/beta + cells. However, both TCR alpha/beta + and TCR gamma/delta + clones (TCR delta 1+) from one RA patient showed antigen-specific lysis. Antigen-specific recognition by a number of CTL lines and clones generated from SF and SM was restricted by HLA-DR molecules. Two Mycobacterium bovis 65-kd heat shock protein (HSP)-specific TCR alpha/beta + SF T cell clones also lysed M phi that had been pulsed with a recombinant human 65-kd HSP. CONCLUSION: Joint inflammation and destruction might be partly attributable to a cross-reaction of mycobacteria-induced cytotoxic T cells with self HSP.

Antibodies, Monoclonal

Limited heterogeneity of T cell receptor variable region gene usage in juvenile rheumatoid arthritis synovial T cells.

The aim of this study was to determine whether synovial fluid (SF) T cells in patients with juvenile rheumatoid arthritis (JRA) are restricted in their T cell receptor (TcR) gene repertoire. The quantitative polymerase chain reaction (QPCR) was used to compare the transcription of V beta and V alpha gene families in freshly isolated SF T cells, in interleukin-2 receptor-positive (IL-2R+) T cells and in peripheral blood (PB) T cells from 18 patients. Significantly less V beta families are detected in SF when compared with PB (p greater than 0.0003). The TcR V beta gene usage by IL-2R+ T cells was even less heterogeneous when compared with freshly isolated SF T cells (p greater than 0.0002). Freshly isolated SF T cells from the left and the right knees of four patients transcribed the same V beta families. Furthermore, we demonstrate that in SF the distribution of certain TcR V beta gene segments in CD4+ and CD8+ T cells differed from that in PB of the same patient. The TcR V alpha usage was studied in IL-2R+ T cells from six patients who had shown restriction in their SF TcR V beta gene usage. Only two to five TcR alpha transcripts were detected in three of these patients while a broad TcR V alpha usage was seen in the other three patients. Sequence analysis of the SF V beta 20 cDNA clones generated from the IL-2R+ T cells of two patients demonstrated an oligoclonal expansion. Taken together, our data could indicate an antigen- and/or superantigen-driven expansion of selected T cells in the synovial compartment.

Adolescent

Lymphocytes from synovial tissue of a boy with X-linked hypogammaglobulinemia and chronic polyarthritis.

Lymphocytes were eluted from synovial tissue of a boy with X-linked hypogammaglobulinemia and chronic polyarthritis. The cell suspension contained 53% lymphocytes and 28% peroxidase-positive, macrophagelike cells, No B lymphocytes, 83% T lymphocytes, and 10% Fc-receptor-bearing lymphocytes were detected. Lymphocyte transformation was induced by polyclonal mitogens (phytohemagglutinin and pokeweed mitogen) whereas no response to antigens (purified protein derivative and Candida albicans antigen) was obtained. The eluted cells displayed antibody-dependent cytotoxicity.

Agammaglobulinemia

Predominance of T lymphocytes in the dermal infiltrate of atopic dermatitis.

Tissue sections from diseased skin of sixteen patients with atopic dermatitis were investigated with haematoxylin-eosin and toluidine-blue staining, with direct immunofluorescence staining using FITC-conjugated antisera against IgG F(ab')2 and IgM, and with the indirect immunofluorescence method utilizing specific rabbit anti-human T lymphocyte antiserum with FITC-conjugated goat anti-rabbit Ig antiserum as the second layer. Furthermore, cryostat sections were investigated in a closed chamber immune adherence method using aminoethylisothiouronium bromide (AET) treated sheep red blood cells to detect E receptors on T lymphocytes, and with various types of coated sheep red blood cells to detect cells with IgG Fc receptors and complement factor C3b receptors. All sections presented dermal perivascular infiltrates of mononuclear cells as judged by haematoxylin-eosin staining. Staining with toluidine-blue demonstrated varying numbers of mast-cells, but in no case pathological increased number. The majority of the infiltrating cells presented rim-like membrane fluorescence with the anti-T antiserum, and the AET treated sheep red blood cells (SRBC) adhered to the infiltrates, thus indicating a predominance of T lymphocytes in the skin infiltrates of atopic dermatitis.

Adolescent

High-density lipoprotein as carrier for amyloid-related protein SAA in rabbit serum.

In this study present evidence that SAA is complexed to high density lipoprotein (HDL) in rabbit serum and is co-isolated with HDL apoproteins. The binding of SAA to HDL seems to be quite strong, judged from affinity chromatography experiments. The studies did not reveal any interaction between SAA and albumin, and there was no evidence that SAA could complex to itself. By isolation of HDL apoproteins, SAA seems to behave like other known apoproteins and may be characterized as an apoprotein that is present in normal serum in very low concentration but increases in concentration under different unphysiological circumstances.

Amyloid

Demonstration of anti-rubella antibody-secreting cells in rheumatoid arthritis patients.

In the present study we describe a plaque-forming cell assay using erythrocytes coated with viral antigen, which detected anti-viral antibody-secreting cells against various viral antigens. These anti-viral antibody-secreting cell were studied in normal individuals with known viral infections and in rheumatoid arthritis patients. Rubella anti-viral antibody-secreting cells were present after induction in the peripheral blood of eight out of ten patients. No plaques were seen before induction. Synovial tissue of seven patients out of ten showed rubella-antigen-specific plaques before induction. In all three patients tested, the numbers of plaques increased after induction. The peripheral blood of only one patient showed plaque-forming cells against mumps virus and cytomegalovirus (CMV) antigen. No other patients showed any plaque against CMV, respiratory syncytial virus, mumps virus, measles virus, adenovirus, and varicella zoster virus antigens. The method appears to be promising in studying viral antibody-secreting cells in human immunopathology.

Antibodies, Viral

The amyloid P-component (protein AP): an integral part of the amyloid substance?

The P-component of amyloid (protein AP) appears to be present in all types of amyloid substance regardless of the clinical category of amyloidosis or the chemical class of the amyloid fibril. The role of protein AP in the formation of amyloid substance has not been established. In a patient with primary amyloidosis, significant amounts of protein AP were found closely associated with the amyloid fibril proteins and was released from the latter only after dissociation and reduction of the amyloid fibril preparation. EDTA seemed to be very effective in releasing protein AP, and it is thought that the close association between the amyloid fibrils and protein AP is calcium-dependent. The very close association between the amyloid fibrils and protein AP suggests that the latter is an integral part of the amyloid substance.

Amino Acid Sequence

Senile cardiac amyloidosis: evidence of two different amyloid substances in the ageing heart.

In a material of seventy-two persons over 70 years of age, forty-seven cases of amyloidosis of the heart were found. In thirty-nine cases, deposits occurred only in the atria (isolated artrial amyloidosis, IAA), while in eight cases amyloid also was seen in the ventricles (senile cardiac amyloidosis, SCA). In some of the latter cases, small amyloid deposits occurred in other organs, especially the lungs. Some definite differences existed between the amyloid substance in SCA and IAA. Thus, tryptophan was demonstrated histochemically in SCA but not in IAA, and, furthermore, amyloid fibrils isolated from patients with IAA lacked protein Asca, the fibril subunit protein of senile cardiac amyloid. It is concluded that the ageing heart may be the target of two different forms of amyloid, one only affecting the atria, while the other is more widespread within the heart and sometimes also is found in other organs.

Aged

Lack of suppressor cell activity in rheumatoid synovial lymphocytes.

Lymphocytes were eluted from the synovial tissue of seventeen patients with rheumatoid arthritis (RA) and one with ankylosing spondylitis. In eight of these patients immunoglobulin production by synovial lymphocytes in the presence and absence of pokeweed mitogen was studied. In nine patients T lymphocytes were isolated from the eluted cells, and the T helper and suppressor cell functions were evaluated in an allogeneic co-culture system. Peripheral blood lymphocytes (PBL) from twenty-eight normal donors were also studied for comparison. Immunoglobulin produced by synovial lymphocytes was higher than in PBL of normal donors. However, the stimulation index of synovial tissue lymphocytes was lower. Most of the normal donors had suppressor cell activity in their peripheral blood, whereas in synovial tissue lymphocytes a statistically significant number of patients did not have any suppressor cell activity. In contrast, the synovial tissue lymphocytes showed helper activity not differing significantly from that of the T lymphocytes from peripheral blood of normal individuals.

Adolescent

Rheumatoid synovial lymphocytes lack concanavalin-A-activated suppressor cell activity.

Synovial lymphocytes eluted by enzyme treatment from eleven patients with rheumatoid arthritis (RA) were investigated for the presence of concanavalin A (Con A)-activated suppressor cell activity as compared with that of peripheral blood lymphocytes of twenty normal donors. In addition, two patients with psoriatic arthritis and juvenile rheumatoid arthritis (JRA) were also investigated. Synovial lymphocytes from the eleven RA patients showed a mean augmentation of 28 +/- 13.30, and thus clearly lacked suppressor activity, whereas the mean suppression in the lymphocytes from the twenty normal donors was 13 +/- 14.40. Synovial lymphocytes from one patient with JRA and one with psoriatic arthritis showed a normal suppressor activity.

Arthritis, Juvenile

Hyporesponsiveness to virus antigens in rheumatoid synovial and blood lymphocytes using the indirect leucocyte migration inhibition test.

Mononuclear cells (MNC) from rheumatoid synovial tissue and peripheral blood were tested plasma pneumonia by the indirect leucocyte migration inhibition test. MNC from the eleven rheumatoid synovial tissues tested had deficient leucocyte inhibitory factor production against all antigens tested for, and this was also the case in the peripheral blood of seven juvenile rheumatoid arthritis patients (JRA). In the peripheral blood of eight rheumatoid arthritis (RA) patients there was also generally low reactivity. However, significant differences in migration indexes were found with rubella viral antigen and with PPD at 5 micrigram/ml when zero-hour and overnight incubations of the culture were compared. In contrast, MNC of peripheral blood of control donors had significant responses to PPD (19/19), mumps virus (7/11), rubella virus (10/19), cytomegalovirus (4/11), and herpes simplex type 1 virus (4/11) antigen after zero-hour culture, and no differences was seen after overnight incubation.

Antigens, Viral

Characterization of amyloid of ageing obese-hyperglycaemic mice and their lean littermates.

Amyloid fibrils, isolated from 18-month-old obese-hyperglycaemic mice and their lean littermates, were characterized immunologically and chemically. The main amyloid fibril subunit protein was protein AA, which cross-reacted completely with an antiserum against amyloid from mice with experimentally induced amyloidosis and had an amino acid composition and N-terminal amino acid sequence identical to that protein. These results indicate that the spontaneously occurring amyloidosis in obese-hyperglycaemic mice and their lean littermates corresponds to human, secondary amyloidosis and may serve as a model for that disease.

Aging

Demonstration of rheumatoid factor idiotypic antigens on peripheral blood B and T lymphocytes from patients with rheumatoid arthritis.

Antisera were raised against three polyclonal IgM rheumatoid factors (RF). After adequate absorptions, the antisera were rendered idiotype-specific, as assayed by haemagglutination technique. By using the anti-idiotype antisera in indirect immunofluorescence on peripheral blood lymphocytes from the patients used as donors for the immunizing RF, it was demonstrated that 3-14% of the lymphocytes were stained, and thus had membrane-bound structures with idiotypic antigens similar to those of the circulating IgM RF of the same patients. While most of these idiotype-positive lymphocyte were B lymphocytes, it was demonstrated in one patient that about 7% of the T lymphocytes also had the same idiotypic antigens.

Arthritis, Rheumatoid

Demonstration of protein AA in subcutaneous fat tissue obtained by fine needle biopsy.

Polarisation microscopy of material obtained by fine needle biopsy of subcutaneous tissue and stained with Congo red is a simple and reliable method for the diagnosis of systemic amyloidosis. It cannot, however, be used to differentiate histologically between different forms of amyloidosis. In the present study extracts of material obtained by fine needle biopsy of subcutaneous fat tissue from 13 patients were examined by double immunodiffusion with an antiserum against protein AA, a unique protein which forms a major part of the fibrils in secondary amyloidosis. Five of the patients showed amyloid deposits round the fat cells by conventional microscopy. In 3 of these, all with rheumatoid arthritis, protein AA was detected. Eight patients without amyloidosis and 2 with myelomatosis and amyloidosis showed no reaction with antiprotein AA antiserum. Thus the material obtained by fine needle biopsy of subcutaneous tissue could be used not only for the histological diagnosis of amyloidosis but also for a classification of systemic amyloidosis into secondary or primary based on the type of amyloid fibril protein involved.

Adipose Tissue